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Background: Cardiopulmonary exercise testing (CPET), the gold-standard method to quantify cardiorespiratory fitness (CRF), is not always feasible due to cost, access, and burden. The usual-paced 400 m long distance corridor walk (LDCW), a measure of mobility among older adults, may provide an alternate method to assess CRF. The purpose of this study was to develop and validate an estimating equation to estimate VO 2 peak from average 400 m walking speed (WS) among participants in the Study of Muscle, Mobility and Aging (SOMMA)., Methods: At baseline, women (58%) and men age 70 years and older enrolled in SOMMA (N = 820, 76.2 ± 4.9 years, 86% Non-Hispanic White) completed a 400 m LDCW (400 m WS = 400 m/completion time in seconds) and symptom-limited maximal CPET (Modified Balke Protocol). VO 2 peak (mL/kg/min) was considered the highest 30-second average oxygen consumption during CPET. Other covariates included: age, sex, race, physical activity (7-day wrist-worn accelerometer), physical function (Short Physical Performance Battery, range 0-12), perceived physical fatigability (Pittsburgh Fatigability Scale, range 0-50), and Borg Rating of Perceived Exertion (RPE, range 6-20) at completion of the 400 m LDCW. Stepwise linear regression was used. Internal validation was completed using data-splitting method (70%; 30%)., Results: Mean VO 2 peak was 20.2 ± 4.8 mL/kg/min and mean 400 m WS was 1.06 ± 0.2 m/s. Each 0.05 m/s increment in 400 m WS was associated with a 0.40 mL/kg/min higher VO 2 peak after covariate adjustment. An estimating equation including 400 m WS, age, sex, race, and RPE was developed. Internal validation showed low overall bias (-0.26) and strong correlation (r = 0.71) between predicted and measured VO 2 peak values. Bland-Altman plot and regression analyses indicated predicted VO 2 peak was an acceptable alternative, despite mean underestimation of 4.53 mL/kg/min among the highly fit., Conclusions: Usual-paced 400 m LDCW strongly correlates with direct measures of CRF during CPET in older adults with lower fitness and can be used to test both fitness and function., (© 2023 The American Geriatrics Society.)

Objectives: Our aim was to examine the impacts of baseline fatigue on the effectiveness of a physical activity (PA) intervention to prevent major mobility disability (MMD) and persistent major mobility disability (PMMD) in participants from the Lifestyle Interventions and Independence for Elders (LIFE) study., Design: Prospective cohort of individuals aged 65 years or older undergoing structured PA intervention or health education (HE) for a mean of 2.6 years., Setting: LIFE was a multicenter eight-site randomized trial that compared the efficacy of a structured PA intervention with an HE program in reducing the incidence of MMD., Participants: Study participants (N = 1591) at baseline were 78.9 ± 5.2 years of age, with low PA and at risk for mobility impairment., Measurements: Self-reported fatigue was assessed using the modified trait version of the Exercise-Induced Feelings Inventory, a six-question scale rating energy levels in the past week. Responses ranged from 0 (none of the time) to 5 (all of the time). Total score was calculated by averaging across questions; baseline fatigue was based on the median split: 2 or higher = more fatigue (N = 856) and lower than 2 = less fatigue (N = 735). Participants performed a usual-paced 400-m walk every 6 months. We defined incident MMD as the inability to walk 400-m at follow-up visits; PMMD was defined as two consecutive walk failures. Cox proportional hazard models quantified the risk of MMD and PMMD in PA vs HE stratified by baseline fatigue adjusted for covariates., Results: Among those with higher baseline fatigue, PA participants had a 29% and 40% lower risk of MMD and PMMD, respectively, over the trial compared with HE (hazard ratio [HR] for MMD = .71; 95% confidence interval [CI] = .57-.90; P = .004) and PMMD (HR = .60; 95% CI = .44-.82; P = .001). For those with lower baseline fatigue, no group differences in MMD (P = .36) or PMMD (P = .82) were found. Results of baseline fatigue by intervention interaction was MMD (P = .18) and PMMD (P = .05)., Conclusion: A long-term moderate intensity PA intervention was particularly effective at preserving mobility in older adults with higher levels of baseline fatigue. J Am Geriatr Soc 68:619-624, 2020., (© 2019 The American Geriatrics Society.)

Objectives: This study aims to investigate the impact of respiratory symptoms in current and former smokers with and without obstructive lung disease (OLD) on all-cause mortality., Design: Secondary analysis in a prospective cohort (the Health, Aging and Body Composition study)., Setting: Memphis, Tennessee, and Pittsburgh, Pennsylvania., Participants: Black and white men and women with a history of current and former smoking (N = 596; 63% male and 37% female) aged 70-79 years followed for 13 years. Participants were categorized into 4 mutually exclusive groups based on symptom profile and forced expiratory volume in the 1st second to forced vital capacity ratio. The groups were Less Dyspnea-No OLD (N = 196), More Dyspnea-No OLD (N = 104), Less Dyspnea-With OLD (N = 162), and More Dyspnea-With OLD (N = 134)., Measurements: All-cause mortality., Results: Overall, 53% in Less Dyspnea-No OLD, 63% in More Dyspnea-No OLD, 67% in Less Dyspnea-With OLD, and 84% in More Dyspnea-With OLD died within the 13- year follow up period (log-rank χ 2  = 44.4, P < .0001). The hazard ratio was highest for participants with OLD, both with (HR =1.91, 95% CI 1.44 - 2.54; P < .0001) and without dyspnea (HR = 1.52, 95% CI 1.15 - 2.02; p = .004). Participants without OLD but with dyspnea had a similar risk of death to subjects who had OLD but fewer symptoms., Conclusions: OLD is associated with high risk of death with different risk profiles based on symptom group. Patients with symptoms of shortness of breath without OLD should be considered an at-risk group given their similar mortality to those with OLD with minimal symptoms. J Am Geriatr Soc 67:2116-2122, 2019., (© 2019 The American Geriatrics Society.)

Objectives: To test whether structured physical activity (PA) is associated with a greater reduction in major mobility disability (MMD) in older persons with metabolic syndrome (MetS) than in those without., Design: Data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter randomized trial of 1,635 persons with assessments every 6 months (average 2.7 years)., Setting: Eight U.S. centers., Participants: Sedentary men and women aged 70 to 89 with functional limitations (N = 1,535); 100 participants were excluded because of missing MetS data., Intervention: Participants were randomized to a moderate-intensity PA program (n = 766) or a health education program (n = 769)., Measurements: MetS was defined according to the 2009 multiagency harmonized criteria. Outcomes included incident MMD (loss of ability to walk 400 m) and persistent MMD (two consecutive MMD diagnoses or one MMD diagnosis followed by death)., Results: Seven hundred sixty-three (49.7%) participants met criteria for MetS. PA reduced incident MMD more than health education did in participants with MetS (hazard ratio (HR) = 0.72, 95% confidence interval (CI) = 0.57-0.91, P = .007) but not in those without MetS (HR = 0.96, 95% CI = 0.73-1.25, P = .75); the test for statistical interaction was not significant (P = .13). PA reduced the risk of persistent MMD in participants with MetS (HR = 0.57, 95% CI = 0.41-0.79, P < .001) but not in those without MetS (HR = 0.97, 95% CI = 0.67-1.41, P = .87). The test for statistical interaction was significant (P = .04)., Conclusion: Moderate-intensity PA substantially reduces the risk of persistent MMD in older persons with functional limitations with MetS but not in those without MetS. Comparable results were observed for incident MMD. The LIFE PA program may be an effective strategy for reducing mobility disability in vulnerable older persons with MetS., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Objectives: To describe the interindividual variability in physical function responses to supervised resistance and aerobic exercise training interventions in older adults., Design: Data analysis of two randomized, controlled exercise trials., Setting: Community-based research centers., Participants: Overweight and obese (body mass index (BMI)≥27.0 kg/m2) sedentary men and women aged 65 to 79 (N=95)., Intervention: Five months of 4 d/wk of aerobic training (AT, n=40) or 3 d/wk of resistance training (RT, n=55)., Measurements: Physical function assessments: global measure of lower extremity function (Short Physical Performance Battery (SPPB)), 400-m walk, peak aerobic capacity (VO2 peak), and knee extensor strength., Results: On average, both exercise interventions significantly improved physical function. For AT, there was a 7.9% increase in VO2 peak; individual absolute increases varied from 0.4 to 4.3 mL/kg per minute, and four participants (13%) showed no change or a decrease in VO2 peak. For RT, knee extensor strength improved an average of 8.1%; individual increases varied from 1.2 to 63.7 Nm, and 16 participants (30%) showed no change or a decrease in strength. Usual gait speed, 400-m walk time, chair rise time, and SPPB improved for the majority of AT participants and usual gait speed, chair rise time, and SPPB improved for the majority of RT participants, but there was wide variation in the magnitude of improvement. Only change in 400-m walk time with RT was related to exercise adherence (correlation coefficient=-0.31, P=.004)., Conclusion: Despite sufficient levels of adherence to both exercise interventions, some participants did not improve function, and the magnitude of improvement varied widely. Additional research is needed to identify factors that optimize responsiveness to exercise to maximize its functional benefits in older adults., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objectives: To evaluate the prevalence of metabolic syndrome (MetS) and its association with physical capacity, disability, and self-rated health in older adults at high risk of mobility disability, including those with and without diabetes mellitus., Design: Cross-sectional analysis., Setting: Lifestyle Interventions and Independence for Elders (LIFE) Study., Participants: Community-dwelling sedentary adults aged 70 to 89 at high risk of mobility disability (Short Physical Performance Battery (SPPB) score ≤9; mean 7.4 ± 1.6) (N = 1,535)., Measurements: Metabolic syndrome was defined according to the 2009 multiagency harmonized criteria; outcomes were physical capacity (400-m walk time, grip strength, SPPB score), disability (composite 19-item score), and self-rated health (5-point scale ranging from excellent to poor)., Results: The prevalence of MetS was 49.8% in the overall sample (83.2% of those with diabetes mellitus, 38.1% of those without). MetS was associated with stronger grip strength (mean difference (Δ) = 1.2 kg, P = .01) in the overall sample and in participants without diabetes mellitus and with poorer self-rated health (Δ = 0.1 kg, P < .001) in the overall sample only. No significant differences were found in 400-m walk time, SPPB score, or disability score between participants with and without MetS, in the overall sample or diabetes mellitus subgroups., Conclusion: Metabolic dysfunction is highly prevalent in older adults at risk of mobility disability, yet consistent associations were not observed between MetS and walking speed, lower extremity function, or self-reported disability after adjusting for known and potential confounders. Longitudinal studies are needed to investigate whether MetS accelerates declines in functional status in high-risk older adults and to inform clinical and public health interventions aimed at preventing or delaying disability in this group., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objectives: To determine the independent effect of long-term physical activity (PA) and the combined effects of long-term PA and weight loss (WL) on inflammation in overweight and obese older adults., Design: Eighteen-month randomized, controlled trial., Setting: The community infrastructure of cooperative extension centers., Participants: Overweight and obese (body mass index >28.0 kg/m(2) ) community-dwelling men and women aged 60 to 79 at risk for cardiovascular disease (CVD)., Intervention: Physical activity + weight loss (PA + WL) (n = 98), PA only (n = 97), or successful aging (SA) health education (n = 93) intervention., Measurements: Biomarkers of inflammation (adiponectin, leptin, high-sensitivity interleukin (hsIL)-6, IL-6sR, IL-8, and soluble tumor necrosis factor receptor 1) were measured at baseline and 6 and 18 months., Results: After adjustment for baseline biomarker, wave, sex, and visit, leptin and hsIL-6 showed a significant intervention effect. Specifically, leptin was significantly lower in the PA + WL group (21.3 ng/mL, 95% confidence interval (CI) = 19.7-22.9 ng/mL) than in the PA (29.3 ng/mL, 95% CI = 26.9-31.8 ng/mL) or SA (30.3 ng/mL, 95% CI = 27.9-32.8 ng/mL) group (both P < .001), and hsIL-6 was significantly lower in the PA + WL group (2.1 pg/mL, 95% CI = 1.9-2.3 pg/mL) than in the PA (2.5 pg/mL, 95% CI = 2.3-2.7 pg/mL) or SA (2.4 pg/mL, 95% CI = 2.2-2.6 pg/mL) group (P = .02)., Conclusion: Addition of dietary-induced WL to PA reduced leptin and hsIL-6 more than PA alone and more than a SA intervention in older adults at risk for CVD. Results suggest that WL, rather than increased PA, is the lifestyle factor primarily responsible for improvement in the inflammatory profile., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

Objectives: To assess the relationship between body mass index (BMI) and waist-hip ratio (WHR) and the clinical end points of cognitive impairment and probable dementia in a cohort of older women enrolled in the Women's Health Initiative Memory Study (WHIMS)., Design: Prospective, randomized clinical trial of hormone therapies with annual cognitive assessments and anthropometrics., Setting: Fourteen U.S. clinical sites of the WHIMS., Participants: Seven thousand one hundred sixty-three postmenopausal women aged 65 to 80 without dementia., Measurements: Annual cognitive assessments, average follow-up of 4.4 years, including classification of incident cognitive impairment and probable dementia. Height, weight, waist, and hip measurements were assessed at baseline, and a waist-hip ratio (WHR) of 0.8 or greater was used as a marker of central adiposity., Results: There were statistically significant interactions between BMI and WHR and incident cognitive impairment and probable dementia with and without adjustment for a panel of cognitive risk factors. Women with a WHR of 0.80 or greater with a BMI of 20.0 to 24.9 kg/m² had a greater risk of cognitive impairment and probable dementia than more-obese women or women with a WHR less than 0.80, although women with a WHR less than 0.80 and a BMI of 20.0 to 24.9 kg/m² had poorer scores on cognitive assessments., Conclusion: WHR affects the relationship between BMI and risk of cognitive impairment and probable dementia in older women. Underweight women (BMI < 20.0 kg/m²) with a WHR less than 0.80 had a greater risk than those with higher BMIs. In normal-weight to obese women (20.0-29.9 kg/m², central adiposity (WHR ≥ 0.80) is associated with greater risk of cognitive impairment and probable dementia than in women with higher BMI. These data suggest that central adiposity as a risk factor for cognitive impairment and probable dementia in normal-weight women., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

Objectives: To determine the effects of a long-term exercise intervention on two prominent biomarkers of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in elderly men and women., Design: Single-blind, randomized, controlled trial: The Lifestyle Interventions and Independence for Elders (LIFE) Trial., Setting: The Cooper Institute, Dallas, Texas; Stanford University, Stanford, California; University of Pittsburgh, Pittsburgh, Pennsylvania; and Wake Forest University, Winston-Salem, North Carolina., Participants: Four hundred twenty-four elderly (aged 70-89), nondisabled, community-dwelling men and women at risk for physical disability., Intervention: A 12-month moderate-intensity physical activity (PA) intervention and a successful aging (SA) health education intervention., Measurements: CRP and IL-6., Results: After adjustment for baseline IL-6, sex, clinic site, diabetes mellitus, treatment group, visit, and group-by-visit interaction, the PA intervention resulted in a lower (P=.02) IL-6 concentration than the SA intervention. Adjusted mean IL-6 at month 12 was 8.5% (0.21 pg/mL) higher in the SA than the PA group. There were no significant differences in CRP between the groups at 12 months (P=.09). Marginally significant interaction effects of the PA intervention according to baseline functional status (P=.05) and IL-6 (above vs below the median; P=.06) were observed. There was a greater effect of the PA intervention on participants with lower functional status and those with a higher baseline IL-6., Conclusion: Greater PA results in lower systemic concentrations of IL-6 in elderly individuals, and this benefit is most pronounced in individuals at the greatest risk for disability and subsequent loss of independence.

Objectives: To describe the relationships between proinflammatory biomarkers and self-reported and performance-based physical function and to examine the effect of weight loss on these markers of inflammation., Design: Randomized, longitudinal, clinical study comparing subjects eating an energy-restricted diet and participating in exercise training with a control group., Setting: Community-base participants for the Physical Activity, Inflammation and Body Composition Trial., Participants: Eighty-seven obese (body mass index (BMI) >30.0 kg/m(2)) adults aged 60 and older with knee pain and self-report of osteoarthritis., Measurements: Inflammatory biomarkers (interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), C-reactive protein, and soluble receptors for TNFalpha (sTNFR1 and sTNFR2)) and self-reported (Western Ontario and McMaster University Osteoarthritis Index questionnaire) and performance-based (6-minute walk distance and stair climb time) measures of physical function at baseline and 6 months., Results: Mean (standard error of the mean) weight loss was 8.7% (0.8%) in the intervention group, compared with 0.0% (0.7%) in the control group. sTNFR1 was significantly less in the intervention group than in the control group at 6 months. sTNFR1 and sTNFR2 predicted stair climb time at baseline. Change across the 6-month intervention for sTNFR2 was an independent predictor for change in 6-minute walk distance., Conclusion: These results indicate that an intensive weight-loss intervention in older obese adults with knee pain can help improve inflammatory biomarkers and that changes in these concentrations showed associations with physical function.

Objectives: To examine whether total and abdominal adiposity are risk factors for the development of chronic heart failure (CHF) in older men and women., Design: Prospective, longitudinal cohort: The Health, Aging and Body Composition study., Setting: Memphis, Tennessee, and Pittsburgh, Pennsylvania, metropolitan areas., Participants: Three thousand seventy-five well-functioning community-dwelling older adults aged 70 to 79., Measurements: Body composition using dual energy X-ray absorptiometry, visceral adipose tissue area using computed tomography, adjudicated CHF., Results: Of the remaining (640 participants excluded from original group of 3,075) 2,435 participants (1,081 men, 1,354 women) without coronary heart disease or CHF at baseline, there were 166 confirmed diagnoses of CHF during the median+/-standard deviation (SD) follow-up of 6.1+/-1.4 years. After adjustment for age, race, sex, site, education, smoking, and chronic obstructive pulmonary disorder, all adiposity variables (body mass index (BMI), adipose tissue mass, percentage body fat, waist-to-thigh ratio, waist circumference, and visceral and subcutaneous abdominal adipose tissue) were significant predictors of the development of CHF. In a model that included waist circumference and BMI, waist circumference was associated with incident CHF (hazard ratio (HR)=1.27, 95% confidence interval (CI)=1.04-1.54 per SD increase, P=.02), but BMI was not (HR=1.08, 95% CI=0.86-1.35). When waist circumference and percentage fat were included together, both variables were significant predictors of CHF (waist: HR=1.17, 95% CI=1.00-1.36 per SD increase, P=.05; percentage fat: HR=1.47, 95% CI=1.16-1.87 per SD increase, P=.002). Stepwise adjustment for inflammation, hypertension, insulin resistance, and diabetes mellitus did not decrease the relative risk of a greater waist circumference for the development of CHF (all HR=1.27-1.32, 95% CI=1.02-1.61 per SD increase)., Conclusion: Abdominal body fat distribution may be a stronger risk factor for CHF than overall obesity.

Objectives: To define clinically relevant cutpoints for usual gait speed and to investigate their predictive value for health-related events in older persons., Design: Prospective cohort study., Setting: Health, Aging and Body Composition Study., Participants: Three thousand forty-seven well-functioning older persons (mean age 74.2)., Measurements: Usual gait speed on a 6-m course was assessed at baseline. Participants were randomly divided into two groups to identify (Sample A; n=2,031) and then validate (Sample B; n=1,016) usual gait-speed cutpoints. Rates of persistent lower extremity limitation events (mean follow-up 4.9 years) were calculated according to gait speed in Sample A. A cutpoint (defining high- (< 1 m/s) and low risk (> or = 1 m/s) groups) was identified based on persistent lower extremity limitation events. The predictive value of the identified cutpoints for major health-related events (persistent severe lower extremity limitation, death, and hospitalization) was evaluated in Sample B using Cox regression analyses., Results: A graded response was seen between risk groups and health-related outcomes. Participants in the high-risk group had a higher risk of persistent lower extremity limitation (rate ratio (RR)=2.20, 95% confidence interval (CI)=1.76-2.74), persistent severe lower extremity limitation (RR=2.29, 95% CI=1.63-3.20), death (RR=1.64, 95% CI=1.14-2.37), and hospitalization (RR=1.48, 95% CI=1.02-2.13) than those in the low-risk group., Conclusion: Usual gait speed of less than 1 m/s identifies persons at high risk of health-related outcomes in well-functioning older people. Provision of a clinically meaningful cutpoint for usual gait speed may facilitate its use in clinical and research settings.

Objectives: To examine the relationship between indicators of inflammation and the incidence of mobility limitation in older persons., Design: Prospective cohort study: the Health, Aging and Body Composition Study., Setting: Pittsburgh, Pennsylvania, and Memphis, Tennessee., Participants: A total of 2,979 men and women, aged 70 to 79, without mobility limitation at baseline., Measurements: Serum levels of interleukin (IL)-6, tumor necrosis factor alpha (TNFalpha), and C-reactive protein (CRP) and soluble cytokine receptors (IL-2sR, IL-6sR, TNFsR1, TNFsR2) were measured. Mobility limitation was assessed and defined as reporting difficulty or inability to walk one-quarter of a mile or to climb 10 steps during two consecutive semiannual assessments over 30 months., Results: Of the 2,979 participants, 30.1% developed incident mobility limitation. After adjustment for confounders (demographics, prevalent conditions at baseline, body composition), the relative risk (RR) of incident mobility limitation per standard deviation (SD) increase was 1.19 (95% confidence interval (CI)=1.10-1.28) for IL-6, 1.20 (95% CI=1.12-1.29) for TNFalpha, and 1.40 (95% CI=1.18-1.68) for CRP. The association between inflammation and incident mobility limitation was especially strong for the onset of more severe mobility limitation and when the levels of multiple inflammatory markers were high. When persons with baseline or incident cardiovascular disease events or persons who were hospitalized during study follow-up were excluded, findings remained similar. In a subset (n=499), high levels of the soluble receptors IL2sR and TNFsR1 (per SD increase: RR=1.23 (95% CI=1.04-1.46) and RR=1.28 (95% CI=1.04-1.57), respectively) were also associated with incident mobility limitation., Conclusion: Findings suggest that inflammation is prognostic for incident mobility limitation over 30 months, independent of cardiovascular disease events and incident severe illness.